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111 Cards in this Set
- Front
- Back
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name four types of repeat elements in DNA
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LINES, SINES, Alu repeats, microsatellites, retrovirus-like elements, DNA transposon 'fossils'
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what is the start codon
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ATG/AUG (aka methionine)
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what would delta F 508 mean
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deletion of the three nt that make up phenylalanine at position 508
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what is TATA box and where is it located
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region in promoter, 25 bp upstream of AUG
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how big is the genome
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3 x 10^9 (haploid genome)
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what is lost when DNA condenses
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H20 molecules
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what is the definition of a nucleoside
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base+sugar
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trick for reviewing geneology patterns: autosomal dominant
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multiple generations (none skipped)
males and females both affected |
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definition nucelotide
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base + sugar + phosphate molecule
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name three examples of repeat sequences
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LINES, SINES, Alu repeats
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what is snRNA
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small nuclear RNA - RNA in the nucleus that helps with mRNA processing, aids transcription factors, maintains telomeres
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average gene size, largest gene and smallest gene
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average gene size: 27kB
largest gene: Tintin 283 kB smallest gene: insulin 1.4 kB |
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where are GC box mostly found
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in more active genes (recall GC in more active transcription areas)
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what is a CAAT box
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it's 80 bp upstream of start, increases efficiency (of transcription?)
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what are enhancers
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enhances transcription, nonspecific location
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what are silencers
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reduces transcription, nonspecific location
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examples of autosomal dominant transmission
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Huntington's,"", achondroplasia and Cowden's
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trick for reviewing geneology patterns: autosomal recessive
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often only single generation
25% risk to offspring |
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examples of autosomal recessive inheritance (3)
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heretidary hemachromatosis
CF PKU |
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trick for reviewing geneology patterns: X-linked dominant
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Males and females affected, most every generation
BUT: no male to male transmission (50% risk to females of affected males; 100% risk to offspring of affected females) |
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example of X-linked dominant inheritance
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one form of vit D resistant ricketts
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trick for reviewing geneology patterns: X linked recessive
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No females affected (carriers only)
No male- to-male transmission |
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examples of X linked recessive inheritance patterns (2)
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hemophilia A and B
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In autosomal recessive, what is the risk of being a carrier if unaffected
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2/3
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trick for reviewing geneology patterns: mitochondrial
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all offspring of females are affected (can't get it from fathers unlike X-linked dominant)
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examples of mitochondrial transmission
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Leber's herditary optic neuropathy, disease affective oxidative phosphorylation
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what is a missense mutation
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point mutation that results in amino acid change but may have no change in protein structure
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what is a nonsense mutation
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introduction of a stop codon
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three examples of missense mutation
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factor V leiden, heretidary hemochromotosis, HbS
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two examples of frameshift mutations
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blood group O, tay sachs
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example of nonsense mutation
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beta-thal in Sardinia
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what is a splice site mutation
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one that adds or removes an intron splice site - changes recognition sequences like GT-AG
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examples of splice site mutations
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some hemoglobinopathies (HgE) and thalassemias
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example of a mutation hot spot
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where CpG islands switch to TpG islands more often than usual
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prototype example of dynamic mutation (unstable trinucleotide repeats) and what goes on
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Fragile X: (CGG)n in 5 UTR of FMR-1; <55, 55-200 premutation, >200 full mutation; tendency to expand during female meiosis
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definition of a polymorphism
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sequence variation in at least 1% of the population
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most restriction enzymes recognize DNA of what length
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4-8 bp
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what are VNTR
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variable number of tandem repeats (minisatellites); head to tail repeats of a core sequence of bp
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what are microsatellites
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2-4 bp repeats, most common type of genetic variation
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genetic mapping based on recombination is measured in what units
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cM
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what affects stringency in S blotting (3)
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heat, denaturing agents (e.g., formamide), pH
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name four labels for staining S. blots
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Radioisotopes (32P, 35S)
Complexing haptens (biotin, DIG) Enzymes Silver staining |
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aa change for sickle cell
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glu to val (alters MST II cut site)
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who passes along full mutation of fragile X
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moms to sons; only mom can convert premutation to full mutation during gametogenesis (meiosis I?)
some daughters can be affected, but more variable |
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do fragile x have shorter survival
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no - generally normal lifespan
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what's the genetic component of fragile X (gene name, how expression occurs)
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gene: FMR-1
normally expressed: brain (and others) in Fra (x): not expressed CGG repeats - normal 6-55; mutation >200 |
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name 5 trinucleotide repeat disorders
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Ms. HoFF (F's are "off" the coding sequence 5')
Fragile X Friedriech's ataxia myotonic dystrophy (3' UTR) CAG's in coding sequence: huntington's spinocerebellar ataxia, type I |
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name four ways in which s blot might still be used
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1. trinucleotide repeats (e.g. fragile x)
2. large deletions (Duchenne muscular dystrophy) 3. point mutations (sickle cell anemia) 4. lymphoid clonal amplification |
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which czome is duchenne muscular dystrophy found
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Xp21
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in use of S blot for determination of lymphoid clonal populations, what percentage of cells are used to consider clonal
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1-5% cells
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what maximum for PCR to amplify (target size)
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~35 kb DNA (used to be ~2 kb)
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average size for primers
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18-35 nt
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3 techniques for minimizing contaminaion by RNases
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baking, DEPH (diethylpyrocarbonate), using RNAse inhibitors
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**name 6 essential reagents for PCR
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1. template DNA
2. primers 3. dNTPs 4. DNA polymerase (e.g. taq1) 5. Mg (1.5mM) 6. buffer |
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efficiency of PCR reaction depends upon (6 factors)
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1. primer selection
2. specificity of reaction 3. appropriate annealing temp 4. Mg concentration 5. quality of DNA template 6. presence of inhibitors (heme) |
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three examples in which RT-PCR can be used to detect gene amplification
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-Bcr/abl in gleevac resistant CML
-her2 neu - n-myc |
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what makes a ddNTP different from dNTP
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lacks 3'OH, resulting in chain termination
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what means of genetic transmission are loss of function mutations
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usually recessive
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what means of genetic transmission are gain of function mutations
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usually dominant inheritance pattern
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what and where is BRCA1
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tumor suppressor gene on czome 17q21; >600 mutations, mostly frameshift leading to protein truncation
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what and where is BRCA2
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tumor suppressor gene on czome 13q12; 450 mutations, variable (ie. frameshift, deletions, insertions, etc.)
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genetics of MEN 1- transmission, gene, location
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AD, Menin 11q13
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genetics of MEN2A transmission, gene, location
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RET 10q11.2
Cysteines 609, 611, 618, 620, 634 |
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genetics of MEN2B transmission, gene, location
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RET, M918T (in tyrosine kinase domain)
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genetics of HNPCC - gene, location
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tumor suppressor gene
MLH1 - 3p21.3 MSH2 - 2p16 if mutation, 80% risk colon ca, 60% uterine |
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genetics of FAP
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AD (near complete penetrance)
APC on 5q21, usually protein truncation truncated protein - since tumor suppressor, leads to increase transcription of downstream gene including MYC and CCND1 |
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extraintestinal FAP sx (gardner's)
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osteomas, dental abnormalities
if with medulloblastoma (think Turcot syndrome) |
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genetics of Li-Fraumeni syndrome
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AD, p53 gene on 17p13
tumor suppressor, expressed in all cells if lost, detectable by FISH (loss of heterozygosity) |
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sx of Li-Fraumeni syndrome
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breast ca, colon ca, stomach, glioblastoma, leukemia and sarcomas
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genetics of hereditary rb
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AD, near complete penetrance
RB1 gene on 13q14 germline mutation, with need to loss of second allele FISH detectable |
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what % of rb is inherited
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40%
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what is "trilateral" RB
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when bilateral RB + pineoblastoma
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what tumors do those with hereditary RB get (7 types)
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RB, pineoblastomas, osteosarcomas, chondrosarcomas, Ewing's sarcoma, leukemia and lymphoma
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Tumor suppressor gene for:
gorlin's basal cell nevus syndrome |
PTC
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Tumor suppressor gene for:
ataxia telangiectasia |
ATM
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Tumor suppressor gene for:
Wilms |
WT1
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Tumor suppressor gene for:
neurofibromatosis I |
NF1
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Tumor suppressor gene for:
neurofibromatosis II |
NF2
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Tumor suppressor gene for:
familial melanoma |
CDKN2A
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Tumor suppressor gene for:
von Hippel-Lindau disease |
VHL
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genetics of Cowden's disease
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AD, germline mutation of PTEN gene, czome 10q23
it is a phosphatase, acts in P13K/act cell cycle arrest and apoptosis pathway, has lipid and protein phosphatase activity |
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sx of Cowden's
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trichilemmomas, colonic hamartomatous polyps, FC changes of breast, MR, macrocephaly
thyroid and breast tumors |
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where are PTEN mutations found (4)
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Cowdens
VATER Proteus syndrome Bannayan-Riley-Ruvalcaba syndrome |
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oncogene examples:
CML |
abl (bcr-abl) - oncogene is on 9
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oncogene examples:
MEN 2a/b |
RET
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oncogene examples:
neuroblastoma |
n-myc
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oncogene examples:
breast (name one) |
her2-neu
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ways that mutations can activate oncogenes (4)
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1. point mutation
2. gene amplification 3. czome translocation to make new transcript 4. moving oncogene to constitutively active region |
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genetics of:
follicular lymphoma (2) |
t(14;18)
bcl2-IgH rearrangement (70-95%) - bcl2 overexpression - blocks apoptosis |
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genetics of:
MALT/marginal zone lymphomas (2) |
trisomy 3 (60% of MALT, lower in marginal zone)
t(11;18)(q21;q21) API2/MLT, associated with resistance to trx for H. pylori, not found in primary large B cell gastric lymphoma |
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genetics of:
transformation to large B-cell lymphoma (from follicular lymphoma) (2) |
associated with 17p deletions (p53) and 9q del (poor prognosis/death)
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genetics of:
splenic marginal zone lymphoma (1) |
allelic loss of 7q21-32 with dysregulation of CDK6 (40%)
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genetics of:
DLBL (2) |
bcl2 is rearranged (30% whether from FL or not)
3q27, involving bcl6 pro-oncogene (30%) |
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genetics of:
Primary mediastinal (thymic) DLBL (3) |
hyperdiploidy
9q+ REL amplification |
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genetics of:
Burkitt lymphoma (5) |
t(8;14)(q24;q32); cmyc to IgHmost common
t(2;8)(p12;q24) Cmyc to light chain kappa (2); minor t(8;22)(q24;11.2) Cmyc to light chain lambda (22); minor 17p (p53) EBV genomes in African/HIV forms |
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genetics of:
CLL/SLL |
trisomy 12 (worse prognosis) - 20%
del13q14 (better prognosis) - 50% del11q with variable breakpoints |
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genetics of:
lymphoplasmacytic lymphoma (LPL)/Waldenstrom's |
t(9;14)(p13;q32) - with rearrangement of PAX-5 gene
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what is PAX5 gene
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encodes a b-cell specific activator protein (BSAP) important in early B cell development
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genetics of:
mantle cell lymphoma (1 big one, 4 minor ones) |
t(11;14) -proto-oncogene PRAD1/bcl1 (11) -IgH (14) (95%)
others: 13q14, +12, 17p deletion, point mutations in ATM gene |
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what does bc1 encode
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cyclin D1 gene
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memory jog:
burkitt - main gene player |
c-myc (located czome 8)
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memory jog:
follicular lymphoma- main gene player |
bcl2 (located czome 18)
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memory jog:
mantle cell lymphoma - main gene player |
bc1 (czome 11)
aka cyclin d1) |
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what can be overexpressed in hairy cell leukemia that is also in mantle cell lymphoma
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cyclin D1 (but for hairy cell leukemia, it is not associated with bcl-1 rearrangement)
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T cell receptor locations
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czome 7: G, B
czome 14: A/D (delta is within A) |
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which has a VJ region and which has a VDJ region of the T cell receptors: A, B, D and G
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VJ: AG
VDJ: BD |
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from where does T cell receptors get their genetic diversity (2)
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VJ (AG) and VDJ (BD) and nt insertions/deletions at junctional regions
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frequent czome breakpoint in T cell lymphomas
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TCL locus 14q32 (within TCR alpha chain?)
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what is a common set of mutations in T-PLL and T-CLL (I think the same...)
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inversion 14 (q11q32) or t(14;14)(q11q32)
this is the TCL locus (within TCRalpha?) and the beginning of TCRalpha |
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cause of adult T cell leukemia/lymphoma (ATLL)
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HTLV1 integrated into geneme (and TCR rearrangements)
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what can be found in extranodal NK/T cell lymphoma, nasal type genetically
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EBV genetically integrated; true of some exranasal cases as well
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